In many drug delivery applications, including the delivery of therapeutic agents, proteins, and genes, it is desirable to provide both temporal and spatial control over drug delivery or durable presence of signaling molecules. A high level of spatio-temporal control is needed to maintain the concentration of the drug at the site of action at a therapeutic level while minimizing undesirable systemic side effects. In addition to providing both controlled and targeted drug delivery; for many applications there must also exist some mechanism for protecting the therapeutic agent from in vivo degradation and inactivation. Consequently, many drug delivery systems (DDSs) composed of drug encapsulated in degradable or non-degradable polymer matrices, and micro- or nanoparticles have been developed. Encapsulating the therapeutic agent in a polymer matrix not only protects the drug from degradation, but also allows for the delivery of a large drug payload, which can be released over an extended period of time.
Drug release from such systems is typically controlled by passive diffusion from the polymer matrix, or a combination of diffusion and matrix degradation. While based on passive mechanisms for providing control over drug delivery, these systems do afford a certain degree of tunability. By altering parameters such as the polymer composition or the crosslink density the degradation rate of the matrix can be controlled. The use of DDSs with multiple layers has also been examined as a means of providing finer control over drug release. Systems that offer an even greater degree of tunability by utilizing more active mechanisms for controlling drug delivery have also been developed. These systems often use external stimuli, such as pH, ionic strength, and/or temperature to further control drug release. However, all of these systems share a number of limitations, stemming from the lack of a selective interaction between the drug and the DDS, that greatly restrict their broad efficacy across a number of different applications.
Without the ability to form selective interactions between the drug and DDS, the ability to tune the system becomes a function of the properties of the polymer matrix (e.g., pore size, degradation rate, sensitivity to changes in pH, ionic strength, or temperature, etc.), which often necessitates the development of multiple designs to meet different applications. This limitation is both inefficient and time consuming, and demonstrates the need for the development of a general platform that can be tuned to different applications independently of its properties. Furthermore, while many of the systems previously described can be used to provide control over the release of a single agent, they are limited in their ability to selectively control the release of multiple agents. The ability to selectively control the release, and thus expression, of multiple agents is especially important in tissue engineering applications that intend to recapitulate the natural tissue regeneration process. In such applications, the DDS must be able to express different bioactive agents at different time points. Thus, the DDS must contain some mechanism for providing selective control over the release of multiple agents. Finally, for the majority of implantable DDSs the drug reservoir is limited. While this may be acceptable, or even desirable for some applications, it is a major drawback for the treatment of chronic conditions (e.g. insulin delivery in diabetes). For such applications, a reloadable drug reservoir is needed. This presents a complicated design criterion as the DDS must be able to selectively interact with and bind the desired drug molecule(s) from the surrounding environment.